On June 8, 2026, Tango Therapeutics announced initial data from an ongoing Phase 1/2 study of vopimetostat in combination with Revolution Medicines’ RAS(ON) inhibitors in patients with MTAP-deleted and RAS-mutant metastatic pancreatic ductal adenocarcinoma (mPDAC). The data included patients treated with vopimetostat plus daraxonrasib or vopimetostat plus zoldonrasib.
What is Vopimetostat?
Vopimetostat is an investigational oral, once-daily, MTA-cooperative PRMT5 inhibitor designed to work selectively in cancer cells with MTAP deletion. MTAP deletions occur in 10–15% of all human cancers, including approximately 40% of pancreatic cancers and 15% of lung cancers. Vopimetostat is being evaluated as monotherapy and in combination clinical studies.
Study Population
As of the May 28, 2026 data cutoff, 59 patients with previously treated MTAP-deleted and RAS-mutant pancreatic ductal adenocarcinoma or non-small cell lung cancer had received a vopimetostat-based combination. Patients were treated with either vopimetostat plus daraxonrasib or vopimetostat plus zoldonrasib. The vopimetostat plus daraxonrasib group included 20 patients with pancreatic ductal adenocarcinoma and 5 patients with non-small cell lung cancer. The vopimetostat plus zoldonrasib group included 34 patients with pancreatic ductal adenocarcinoma.
All patients had advanced disease. Liver metastases were present in 70% of patients in the daraxonrasib pancreatic cancer arm and 77% of patients in the zoldonrasib arm. More than half of patients received treatment as third-line therapy.
Vopimetostat Plus Daraxonrasib
In the vopimetostat plus daraxonrasib dose-escalation arm, patients received vopimetostat 200 mg or 250 mg once daily plus daraxonrasib 100 mg once daily.
As of the data cutoff, 12 patients with pancreatic ductal adenocarcinoma and 3 patients with non-small cell lung cancer were response evaluable with at least 14 weeks of follow-up. In response-evaluable patients with pancreatic ductal adenocarcinoma, the objective response rate was 92%, with responses in 11 of 12 patients. Nine of the 11 responses were confirmed.
The 6-month progression-free survival rate was 90%, the disease control rate was 100%, and median progression-free survival had not yet been reached. In response-evaluable patients with non-small cell lung cancer, the objective response rate was 100%, with 3 of 3 responses confirmed.
Read more about Daraxonrasib on OncoDaily.
Safety of Vopimetostat Plus Daraxonrasib
The vopimetostat plus daraxonrasib combination was generally well tolerated across all dose levels, with no new safety signals observed.
Most adverse events were Grade 1 or 2. The most common treatment-related adverse events were rash, stomatitis or mucositis, and diarrhea. There were no related Grade 4 or Grade 5 adverse events.
No dose-limiting toxicities were reported at dose level 1, which included vopimetostat 200 mg and daraxonrasib 100 mg. At dose level 2, which included vopimetostat 250 mg and daraxonrasib 100 mg, 3 dose-limiting toxicities were reported in 2 patients. These included one case of Grade 3 rash and one case of Grade 3 stomatitis and fatigue. There were 2 dose reductions at dose level 1 and 1 dose reduction at dose level 2. There were no discontinuations due to adverse events.
Vopimetostat Plus Zoldonrasib
The study also evaluated vopimetostat plus zoldonrasib in patients with pancreatic ductal adenocarcinoma with MTAP deletion and KRAS G12D mutation.
Patients received vopimetostat 200 mg or 250 mg once daily plus zoldonrasib 600 mg or 1200 mg once daily. As of the May 28, 2026 data cutoff, 27 patients were response evaluable with at least 14 weeks of follow-up. The objective response rate was 52%, with responses in 14 of 27 patients. Ten of the 14 responses were confirmed. The 6-month progression-free survival rate was 74%, and the disease control rate was 96%.
Safety of Vopimetostat Plus Zoldonrasib
The vopimetostat plus zoldonrasib combination was generally well tolerated at all dose levels, with no new safety signals observed. Most adverse events were Grade 1 or 2. The most common treatment-related adverse events were nausea and vomiting. There were no related Grade 4 or Grade 5 adverse events, no dose-limiting toxicities, 1 dose reduction, and no discontinuations due to adverse events.
You can also read about the RASolute 302 Trial at the ASCO 2026 Plenary Session on OncoDaily.
Expert Highlight
Brian Wolpin, MD, Director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute, said:
“Pancreatic cancer remains a largely intractable disease and an area where patients desperately need new therapies,”
He continued:
“In the front-line setting, chemotherapy has long been the standard of care, yet it presents significant tolerability challenges and overall limited efficacy against this aggressive disease. Building on the monotherapy activity already shown by these investigational PRMT5 and RAS(ON) targeted therapies, these early combination data demonstrated the potential to meaningfully reshape how we treat this disease with a precision-guided, chemotherapy-free approach.”
Development Plans
Based on these data, Tango Therapeutics stated that it intends to advance the vopimetostat plus daraxonrasib combination into Phase 3 development for patients with MTAP-deleted pancreatic cancer.
Subject to feedback from regulatory authorities, the company plans to initiate a Phase 3 randomized-controlled trial in front-line pancreatic cancer and evaluate opportunities to advance the second-line combination toward a registration-stage study.
Tango Therapeutics also listed several anticipated milestones for the second half of 2026, including finalizing the Phase 3 trial design in front-line pancreatic cancer, disclosing vopimetostat lung cancer monotherapy data, releasing initial TNG456 glioblastoma data, presenting second- and third-line pancreatic cancer combination data at a scientific conference, and initiating a Phase 1/2 vopimetostat plus ERAS-0015 combination study.
Takeaway
Initial Phase 1/2 data from Tango Therapeutics showed a 92% objective response rate and a 90% 6-month progression-free survival rate with vopimetostat plus daraxonrasib in response-evaluable patients with MTAP-deleted and RAS-mutant pancreatic ductal adenocarcinoma. Tango Therapeutics plans to advance the combination toward Phase 3 development in MTAP-deleted pancreatic cancer.
The full press release is available on the Tango Therapeutics website.